NM_001395656.1:c.1072-1026C>T

Variant names:

• chr3-77549792-C-T
• rs1666130
• NM_001395656.1:c.1072-1026C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395656.1(ROBO2):​c.1072-1026C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,746 control chromosomes in the GnomAD database, including 23,866 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (23866 hom., cov: 32)
• Consequence: ROBO2 NM_001395656.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48
• Publications: 6 publications found

Genes affected

ROBO2 (HGNC:10250): (roundabout guidance receptor 2) The protein encoded by this gene belongs to the ROBO family, part of the immunoglobulin superfamily of proteins that are highly conserved from fly to human. The encoded protein is a transmembrane receptor for the slit homolog 2 protein and functions in axon guidance and cell migration. Mutations in this gene are associated with vesicoureteral reflux, characterized by the backward flow of urine from the bladder into the ureters or the kidney. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ROBO2 Gene-Disease associations (from GenCC):

• vesicoureteral reflux 2

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial vesicoureteral reflux

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROBO2	NM_001395656.1	c.1072-1026C>T		intron_variant	Intron 8 of 27	ENST00000696593.1	NP_001382585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROBO2	ENST00000696593.1	c.1072-1026C>T		intron_variant	Intron 8 of 27		NM_001395656.1	ENSP00000512738.1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 84924 AN: 151628 Hom.: 23856 Cov.: 32

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.594

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.560 AC: 84969 AN: 151746 Hom.: 23866 Cov.: 32 AF XY: 0.561 AC XY: 41591 AN XY: 74132

African (AFR) AF: 0.583 AC: 24128 AN: 41410

American (AMR) AF: 0.589 AC: 8958 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2349 AN: 3472

East Asian (EAS) AF: 0.524 AC: 2692 AN: 5134

South Asian (SAS) AF: 0.564 AC: 2717 AN: 4814

European-Finnish (FIN) AF: 0.496 AC: 5221 AN: 10536

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36939 AN: 67860

Other (OTH) AF: 0.591 AC: 1245 AN: 2108

Alfa AF: 0.557 Hom.: 60684

Bravo AF: 0.569

Asia WGS AF: 0.543 AC: 1887 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Benign	0.50
PhyloP100		2.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1666130; hg19: chr3-77598943; COSMIC: COSV59916642;